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PubMed2004

[Comparison of steroid metabolism markers in endometrium of women with endometriosis, endometrial hyperplasia and without pathological changes of endometrium].

OBJECTIVE: To find out any relationship between presence of P450 aromatase and estrogen (ER) and progesterone (PR) receptors in eutopic endometrium of women with and without endometriosis and in estrogen-dependent gynecologic lesions (endometrial hyperplasia and endometriosis). DESIGN: Retrospective study. SETTING: Sikl's Institute of Pathology, Department of Gynecology and Obstetrics, University Hospital and Medical Faculty in Pilsen, Charles University. METHODS: The examined samples were obtained from patients of Department of Gynecology and Obstetrics, University Hospital and Medical Faculty in Pilsen (2001-2002) and elaborated in Sikl's Institute of Pathology, University Hospital and Medical Faculty in Pilsen. There were four experimental groups: endometrial hyperplasia, endometriosis and eutopic endometrium of women with and without endometriosis. P450 arom, ER and PR were detected by using immunohistochemical methods with specific antibodies. RESULTS: P450 aromatase was detected in a higher amount in endometriosis, hyperplasia and some samples of metaplasia. Estrogen and progesterone receptors were detected in all examined tissues. Number and spreading of ER and PR depend on the phase of the cycle. Lower number of ER was found in atrophic and metaplastic endometrium and in atypic hyperplasia. There was not found any direct relationship between presence of P450 aromatase and both types of receptors. CONCLUSION: Steroid metabolism in examined pathologically changed tissues is due to molecular aberrations regulated on the local level. It is not possible to use detection of P450 aromatase as a diagnostic test for pelvic endometriosis.

Adult↗
PubMed1992

[Hysteroscopy in midluteal phase of human endometrium evaluation of functional aspect of the endometrium].

The purpose of this study is to evaluate the possibility of hysteroscopic assessment of functional aspects of the human endometrium. Hysteroscopic findings were classified according to the characteristics of the endometrial glandular opening (GO) and vascular development (V). Thirty-six women with a regular menstrual cycle were evaluated. Of these, ring type GO and type 2 V (moderately developed branching vessels) were seen only after the 17th menstrual day. Of 9 cases on the 21st to the 24th day, 7 had ring type GO, and 5 had type 3 V (well developed varicose-like vessels). Fifty-five infertile women with a regular menstrual cycle were evaluated in the midluteal phase. Of these, 32 cases had ring type GO and type 3 V (classed as group 1), and 23 cases had another type of GO and V (classed as group 2). The number of women whose serum progesterone level was lower than 7 ng/ml was larger in group 2 (p less than 0.05). Both the mean endometrial thickness and maximum follicular diameter measured by ultrasonography were greater in group 1 (p less than 0.01). These results strongly suggest that the hysteroscopic assessment of functional aspects of the endometrium is possible, and the appearance of ring type GO and type 3 V is the result of normally functioning midluteal endometrium.

Adult↗
PubMed1996

Aging of the human endometrium: peri-implantation phase endometrium does not show any age-dependent variation in lectin binding.

OBJECTIVE: To evaluate if the peri-implantation endometrium shows age variations in lectin patterns, which suggest possible age variations in embryo-maternal recognition. STUDY DESIGN: Peri-implantation endometria of younger ( < 30 years of age: n = 13) and older ( > 40 years of age: n = 17) normally menstruating women was studied. Endometrial specimens were routinely fixed in buffered formaline and embedded in paraffin. Sections (5 microns) were studied using seven lectins: DBA (Dolicus biflorus, binding specificity alpha-D-GalNAc), PNA (Arachis hypogea, binding specificity D-Gal (beta 1 --> 3)-D-GalNAc), SBA (Glycine max binding specificity alpha/beta-D-GalNAc > D-Gal), WGA (Triticum vulgare binding specificity (alpha-D-GlcNAc)n and sialic acid), ConA (Canavalia ensiformis binding specificity alpha-D-Man > alpha-D-Glc), LTA (Lotus tetragonolobus binding specificity alpha-L-fucose) and UEA 1 (Ulex europaeus binding specificity alpha-L-fucose). RESULTS: No significant differences were found in the glycoconjugates sugar residue content and distribution between the endometria of women < 30 years of age and those of women > 40. CONCLUSIONS: Our results suggest that human endometrium does not age, at least while cyclic hormonal stimulation and menstruation are present.

Adult↗
PubMed1998

Involvement of cyclin-dependent kinase inhibitor p27Kip1 in growth inhibition of endometrium in the secretory phase and of hyperplastic endometrium treated with progesterone.

A cyclin-dependent kinase (cdk) inhibitor, p27Kip1 (p27), binds to the cyclin E-cdk2 complex and functions as a suppressor of cell cycle promotion. Here, the involvement of p27 in the growth of normal human endometrium was immunohistochemically studied, and the findings were compared with those of Ki-67, cyclin E and cdk2. In addition, to elucidate the effect of progesterone on the expression of p27, tissues from patients with endometrial hyperplasia were examined before and after the administration of medroxyprogesterone acetate (MPA) for the treatment of this disease. In the glandular cells of the normal endometrium, p27 was negligible during the proliferative phase, whereas it was markedly increased in the secretory phase. The staining pattern of Ki-67 was the reverse. Cyclin E/cdk2-positive cells were observed throughout the menstrual cycle. In the secretory phase, the cyclin E/cdk2-positive cells were also positive for p27, suggesting an interaction between these molecules. Stromal cells, especially in the basalis, showed a consistent expression of p27 throughout the menstrual cycle. The expression of p27 in hyperplastic epithelia before the MPA treatment was negligible, whereas it was greatly increased after the treatment. The Ki-67 positivity decreased after the treatment. These findings suggest that p27 is involved in the progesterone-induced growth suppression of normal and hyperplastic endometria.

Adult↗
PubMed2002

Stage-specific expression of the intermediate filament protein cytokeratin 13 in luminal epithelial cells of secretory phase human endometrium and peri-implantation stage rabbit endometrium.

In preparation for blastocyst implantation, uterine luminal epithelial cells express new cell adhesion molecules on their apical plasma membrane. Since one mechanism epithelial cells employ to regulate membrane polarity is the establishment of specific membrane-cytoskeletal interactions, this study was undertaken to determine if new cytokeratin (CK) intermediate filament assemblies are expressed in endometrial epithelial cells during developmental stages related to blastocyst implantation. Type-specific CK antibodies were used for immunocytochemical and immunoblot analyses of 1) intermediate filament networks of the endometrial epithelium during embryo implantation in rabbits and 2) proliferative and secretory phases of the human menstrual cycle. CK18, a type I CK found in most simple epithelia, was expressed in all luminal and glandular epithelial cells of both the human and rabbit endometrium at all developmental stages analyzed; it was also strongly expressed in trophectoderm of the implanting rabbit blastocyst. In contrast, CK13, another type I cytokeratin, exhibited a regulated expression pattern in luminal, but not glandular, epithelial cells of secretory phase human and peri-implantation stage rabbit endometrium. Furthermore, in the rabbit implantation chambers, CK13 was predominantly localized at the cell apex of luminal epithelial cells, where it assembled into a dense filamentous network. These data suggest that the stage-specific expression of CK13 and a reorganization of the apical intermediate filament cytoskeleton of uterine luminal epithelial cells may play important functions in preparation for the implantation process.

Animals↗
PubMed1980

Specific regulation by steroid hormones of protein kinases in the endometrium. 1. Alteration by estrogen and progesterone in levels of protein kinases in rabbit endometrium.

The alteration in activities of multiple protein kinases has been studied in the endometrium of a rabbit treated with estrogen and progesterone. The administration of estrogen or progesterone to the castrated rabbit resulted in a remarkable increase of total activity in the cytosol fraction of the endometrium. The administration of estrogen caused an increase of type I adenosine-3',5'-monophosphate-dependent (cAMP-dependent) protein kinase and a slight decrease of type II cAMP-dependent protein kinase. In contrast, the treatment with progesterone after priming administration of estrogen brought about an increase of type II cAMP-dependent protein kinase and a decrease of type I cAMP-dependent protein kinase. Therefore, the activity ratio of type II to type I decreased by estrogen and increased by progesterone. The simultaneous administration of cycloheximide abolished the stimulatory effect of respective hormones on the level of each protein kinase. The activity profile of protein kinases on DEAE-cellulose column after ovulation caused by the administration of human chorionic gonadotropin to a non-castrated rabbit was similar to that of the rabbit treated with progesterone. The results presented demonstrate the specific regulation by the steroid hormones of de novo synthesis of protein kinases in the target organ.

Animals↗
PubMed1980

Specific regulation by steroid hormones of protein kinases in the endometrium. 2. Alteration in levels of protein kinases in human endometrium during the menstrual cycle.

The alteration in the levels of multiple protein kinases has been studied in human endometrium during the menstrual cycle. Protein kinases were examined in the cytosol fraction and separated by DEAE-cellulose column chromatography. The level of type I adenosine 3',5'-monophosphate-dependent (cAMP-dependent) protein kinase was higher than that of type II cAMP-dependent protein kinase at the proliferative phase. At the late secretory phase, type I cAMP-dependent protein kinase markedly decreased, whereas type II cAMP-dependent protein kinase remained at the same level. Therefore, type II cAMP-dependent protein kinase was exclusively predominant at this phase. cAMP-dependent and cAMP-independent protein kinases with protamine increased more at the late secretory phase than at the proliferative phase. The results presented demonstrate a specific alteration in protein kinase activities during the menstrual cycle and are compatible with those obtained in rabbit endometrium (the preceding paper).

Adult↗
PubMed2004

Coexpression of fractalkine and its receptor in normal human endometrium and in endometrium from users of progestin-only contraception supports a role for fractalkine in leukocyte recruitment and endometrial remodeling.

Leukocytes are critical mediators of endometrial remodeling, but the mechanisms by which leukocyte subpopulations enter the uterus are currently unknown. Endometrial leukocytes have no genomic progesterone receptors; thus, we hypothesized that leukocyte migration is induced indirectly by progesterone-regulated chemokines. Fractalkine (CX3CL1), a chemotactic membrane-bound adhesion factor, and its receptor (CX3CR1) were assessed by immunohistochemistry in endometrial samples across the menstrual cycle, in early pregnancy, and in women using progestin-only contraceptives. Fractalkine was localized predominantly to glandular epithelial and decidualized stromal cells, with the highest staining intensity in the secretory phase and early pregnancy. It was also detected in subpopulations of endometrial leukocytes (macrophages and uterine NK cells), with maximal numbers during the proliferative phase and early pregnancy. CX3CR1 was similarly colocalized to the glandular epithelium and decidualized stromal cells, with the highest expression in the secretory phase. CX3CR1-positive leukocytes (macrophages and neutrophils) were in greatest abundance during the menstrual phase. In the endometrium of women using progestin-only contraceptives, immunoreactive fractalkine was markedly reduced in the glandular epithelium, but was increased in decidualized stroma and infiltrating leukocytes. These findings support a number of roles for fractalkine in the endometrium, in the secretory phase, in early pregnancy, and when influenced by progestin-only contraceptives.

CX3C Chemokine Receptor 1↗
PubMed1978

[Progesterone-induced changes of the endometrium and cervix mucosa in glandular, cystic hyperplasia of the endometrium].

In a period of 5 years 116 specimens were collected with various techniques from patients with the homologous type of cystic-glandular hyperplasia of the endometrium. These were systematically studied with a view to identifying a potential progesteron effect on the morphology of the endometrial and, given sufficient material, cervical mucosa. While the endometrium was examined for discrete areas with signs of secretion, attention in cervical specimens was directed to the potential presence of focal alveolar proliferations of cervical glands with basal cell hyperplasia (socalled cribriform polypoid hyperplasia). Progesteron-induced changes of major endometrial areas were found to be present in 6,9% of cases; the "cribriform polypoid hyperplasia" involving the cervical mucosa was seen in 9 of 43 cases (20,9%) with adequate cervical specimens. In 2 of the patients with progesterone-induced cervical changes luteinized follicular epithelium in the ovaries was indicative of effective endocrine activity. The different action of progesterone on the endometrial versus the cervical mucosa is discussed on the basis of katamnestic studies.

Adult↗
PubMed1997

[The effect of the histological condition of the endometrium on fluid absorption during trans-cervical endometrium resection].

The aim of the study was to assess the effect of the number of endometrial and myometrial vessels on fluid absorption. Operative details and histology results (endometrium chips and myometrial biopsy) of fifty-four consecutive patients undergoing transcervical endometrial resection were analyzed. Thirteen of the 54 patients had hormonal pretreatment using 600 mg/day danazol (n = 11) or norethisterone 10 mg/day (n = 2) for four weeks before procedure. Simultaneous myomectomy were performed on 17 patients. A positive correlation was found between the number of endometrial vessels and volume of fluid absorption, although due to the small study population the result is not significant [p = 0.087, r = 0.29, CI (95%) for r: 0.218 to 0.377]. The correlation with myometrial vessels was found to be negative [p = 0.1, r = -0.39, CI (95%) for r: -0.527 to -0.262]. Patients with hormonal pretreatment absorbed less fluid, but not in a significant amount. Simultaneous myomectomy has no effect on absorption. There is only a poor correlation between fluid absorption during endometrial resection and the number of vessels in the endometrium and myometrium. The authors emphasize the importance of continuous monitoring of fluid dynamics.

Absorption↗
PubMed1990

Peritoneal keratin granulomas with carcinomas of endometrium and ovary and atypical polypoid adenomyoma of endometrium. A clinicopathological analysis of 22 cases.

Twenty-two cases of keratin granulomas of the peritoneum associated with endometrioid adenocarcinoma with squamous differentiation of the endometrium, the ovary, or both, and with an atypical polypoid adenomyoma of the endometrium were reviewed. Follow-up data were available in 18 cases. Twelve patients were well and disease free 13 months to 15.2 years postoperatively; one patient died of unrelated disease 21 years postoperatively; three patients were tumor free with a short duration of follow-up; one patient, who had a stage Ic ovarian tumor, died of pulmonary embolism during the treatment of recurrent tumor 1 year after operation; and a final patient, who had been followed for 3 months after operation for stage IV disease, was alive with residual tumor. At least six patients with stage I carcinomas were treated with postoperative irradiation because the granulomas had raised a suspicion of advanced disease. Follow-up data on the patients in this series suggest that peritoneal keratin granulomas have no prognostic significance and should be distinguished from viable tumor implants on microscopic examination.

Adenocarcinoma↗
PubMed1984

Fluid and protein clearance in the rat endometrium. Part II: Ultrastructural evidence for the presence of alternative, non-lymphatic clearance mechanisms in the rat endometrium.

In the rat endometrium, resident macrophages and exudate phagocytes ensure proteolysis by means of phagocytosis, macro- and micropinocytosis. Using exogenous tracer particles no ultrastructural evidence could be obtained for the occurrence of endometrial prelymphatics. It is suggested that the free tissue fluid may be drained via the fenestrated (probably venous) blood capillaries.

Animals↗
PubMed1998

Immunolocalization of Le(y) oligosaccharide in endometrium during menstrual cycle and effect of early luteal phase mifepristone administration on its expression in implantation stage endometrium of the rhesus monkey.

Changes in carbohydrate expression on endometrial and blastocyst cell surfaces may play a critical role in the process of implantation. Le(y) is an oligosaccharide antigen which has been shown to be involved in blastocyst attachment in the mouse. In the present study, immunohistochemical distribution of Le(y) in endometrium during proliferative and secretory phases of normal menstrual cycles in the rhesus monkey was examined. Endometrial samples were collected on cycle days 7 (n=4), 13 (n= 4), 16 (n=4), 20 (n=4) and 25 (n=3). There was a gradual increase of Le(y) in luminal surface from proliferative to periovulatory (P < 0.001), and from periovulatory to postovulatory (P < 0.05), phases. Le(y) then remained constant in the midsecretory phase and decreased (P < 0.01) during the premenstrual phase. Le(y) score in glands did not change between the phases, except in midsecretory phase when it was higher than that in other phases (P < 0.05). The stromal compartment showed no statistically significant changes. The profiles of endometrial Le(y) on day 6 after ovulation in mated fecund cycles with or without early luteal phase mifepristone treatment were also examined. Females were allowed to cohabit with males during days 8-16 of their ovulatory cycles and were injected s.c. with vehicle (n=7) only, or with a single dose of mifepristone (2 mg/kg body weight; n=8) on day 2 after ovulation. Significant decreases in the area and optical absorption of immunoprecipitate were observed in the epithelial compartment (P < 0.01) following mifepristone treatment. There was no change in the stromal compartment either in area or in optical absorption of immunoprecipitate for Le(y) with or without mifepristone treatment. The expression of Le(y) in the endometrial epithelial compartment appears to be influenced by progesterone and may be associated with endometrial receptivity prior to implantation in the rhesus monkey.

Animals↗
PubMed1989

The binding of peroxidase-labelled lectins to human endometrium in normal cyclical endometrium and endometrial adenocarcinoma.

The nature of endometrial glycoconjugates throughout the menstrual cycle was investigated using a panel of lectins directed against specific sugar groups. This approach was also applied to a series of endometrial adenocarcinomas the findings for which were compared with those of normal controls. A change in the expression of glycosubstances was found in relation to the phase of the menstrual cycle; that there was increasing sialylation of terminal galactose groups during the secretory phase. This change may be influenced by progesterone. One group of endometrial adenocarcinomas exhibited binding patterns similar to those seen in secretory endometrium and this may be related to progesterone receptor state. Expression of fucose containing glycosubstances was identified in half of the carcinomas but not in the normal control tissue, thus indicating that a change in fucosylation occurs with endometrial neoplasia. None of the lectin binding patterns, however, correlated with variables in the patients themselves or within the tumours.

Adenocarcinoma↗
PubMed1977

[The hyperplasia forms of the endometrium and their correlations to the endometrium carcinoma (author's transl)].

In cases of endometrial carcinoma where hysterectomy was performed, we examined histologically the marginal endometrium. For comparison we formed a control group of women of the same age. In the age between 45 and 65 adenomatous hyperplasia in the cancer group is found significantly more often. The glandular-cystic hyperplasia is found more frequently in the age group beyond 55, especially in women beyond 65. The simultaneous incidence of adenomatous hyperplasia and endometrial carcinoma suggests this form of hyperplasia being precancerous. Before the menopause the glandular-cystic hyperplasia does not seem essential for the origin of the endometrial cancer. It is not yet known why the glandular-cystic hyperplasia is found more frequently in postmenopausal women with endometrial carcinoma. The role of the estrogenic hormones as agents possibly forming a good terrain for the endometrial cancer is discussed.

Aged↗
PubMed1991

[Mixed mullerian tumours of the endometrium. Retrospective study, with prognostic aims, comparing their evolution to that of adenocarcinomas of the endometrium].

Mixed Mullerian Tumours (MMT) of the endometrium have a bad reputation as far as prognosis is concerned. We have studied 34 cases of MMT treated between 1976 and 1988 and have compared their outcome with a matched series of 68 cases of adenocarcinoma (ADC). These were taken out of 880 cases of ADC treated during this period of time after matching them for the stage, the type of treatment, the year of treatment and the age of the patient. The curves of survival and the totals of survival were determined using Kaplan-Meier's method and also compared using Logrank's test. The 5-years overall survival was 18% for MMT as against 55% for ADC (p less than 0.001). The difference was equally significant statistically in terms of specific survival without recurrences. The 16 patients in stages I and II who were treated with the same protocol as used for ADC were matched against 32 cases of ADC taken out of the 680 cases ADC in stages I and II and treated by the same protocol (84%). After five years MMT had a higher number of survivors (35% overall, 45% with specific survival and 35% without recurrences), but the difference with survival of ADC was as significant (respectively 75, 85, 85%). Recurrences of MMT were frequent (62%), with metastases in 9 out of 10 and early (50%), in every respect opposed with recurrences of ADC (16%) which were in three out of five cases localized and late (after 10 months). These figures make one have to think of modifying the way MMT is treated. External pelvic radiotherapy should be carried out before any other treatment. The place for other methods of therapy is to be discussed.

Adenocarcinoma↗